Capacitation of mouse sperm is modulated by gamma-aminobutyric acid (GABA) concentration

Abstract

In mammals, ejaculated sperm acquire their fertilizing ability during migration through the female reproductive tract, which secretes several factors that contribute to sperm capacitation. Gamma-aminobutyric acid (GABA) is a well-known neurotransmitter in the central nervous system, but additionally enhances the sperm acrosome reaction in the rat and cow. However, the detailed effects of GABA concentration on sperm function remain unclear. In this study, we detected the presence of the GABA type A receptor (GABA A) in mouse epididymal sperm by western blot analysis and in the sperm acrosome by immunocytochemistry. We also investigated the effects of GABA on sperm fertilizing ability. We found that GABA facilitated the tyrosine phosphorylation of sperm proteins, which is an index of sperm capacitation. GABA also promoted the acrosome reaction, which was suppressed by a selective GABA A receptor antagonist. We then found that the effective GABA concentration for the acrosome reaction corresponds to sperm concentration, but we did not detect any marked effect of GABA on sperm motility using a computer-assisted sperm analysis system. Using immunohistochemistry, we also detected GABA expression in the epithelia of the mouse uterus and oviduct. Furthermore, we found that the mRNA levels of glutamate decarboxylase ( Gad ), which generates GABA from L-glutamate, were higher in the oviduct than in the uterus, and that Gad mRNA levels were higher at estrus than at the diestrus stage. These results indicate that the GABA concentration can act as a modulator of the acrosome reaction and sperm capacitation in the female reproductive tract.

Expression and Possible Role of Nicotinic Acetylcholine Receptor ε Subunit (AChRe) in Mouse Sperm

“…Recently, a number of neurotransmitters have been reported to be involved in sperm functions. Several studies have reported that the receptors for neurotransmitters, such as dopamine [ 7 ], serotonin [ 8 ], gamma-aminobutyric acid (GABA) [ 9 ], and neurotensin [ 10 , 11 ] are present on mammalian sperm, and the ligands corresponding to their receptors are thought to regulate sperm capacitation and/or AR. In this study, we focused on ACh, one of its receptors, nAChR, and one of its subunits, AChRe.…”

“…These findings suggest that the AR is induced during the migration from isthmus to ampulla of the oviduct, indicating that the timing of sperm AR in the oviduct is elaborately regulated. Several factors in the oviduct, such as neurotensin and GABA, are already known to promote AR [ 9 , 11 ]. Thus, ACh may work together with other enhancers of AR to regulate sperm-inducing AR at the optimal time for fertilization.…”

“…Factors secreted from the female reproductive tissues promote sperm protein tyrosine phosphorylation or remove cholesterol from the sperm cell membranes [ 5 , 6 ], suggesting that numerous factors can modulate sperm functions, such as capacitation and acrosome reaction (AR). Recently, several neurotransmitters have been reported to be involved in these sperm functions [ 7 , 8 , 9 , 10 , 11 ].…”

High mRNA expression of GABA receptors in human sperm with oligoasthenoteratozoospermia and teratozoospermia and its association with sperm parameters and intracytoplasmic sperm injection outcomes

“…Several subunits of GABA A and B receptors have been detected in sperm [ 2 - 5 ]. The GABA A receptor alpha 1 (α1) subunit is localized on the head of sperm, as well as the GABA B receptor R2 subunit [ 6 , 7 ]. Although the specific localization of the GABA receptor is not clearly defined, there is evidence that the GABA receptor alpha subunit is localized in the equatorial segment of the human sperm head [ 8 ].…”

“…Although the specific localization of the GABA receptor is not clearly defined, there is evidence that the GABA receptor alpha subunit is localized in the equatorial segment of the human sperm head [ 8 ]. Activation of the GABA A receptor, a ligand gated-chloride ion channel receptor, induces hyperpolarization of the cell membrane, whereas the GABA B receptor, a G-protein-coupled receptor, is involved in the opening of calcium and potassium channels [ 7 ]. Many studies investigated the role of GABA and its receptors in sperm functions that are important for fertilization.…”